Blanc was born in Alès, France. His career started at Montpellier, where he signed his first professional contract in 1983. A very technical, yet slow player, he played as an attacking midfielder and helped the club get promoted to Division 1 in 1987. Only a few years later did he settle as a defender following the advice from Michel Mézy, a position in which his physical stature (1.91 m, 82 kg) and his temper would prove invaluable. His game being perfectly fitted for the French league, he managed to score at least 12 goals in every season at Montpellier, for the most part penalties and headers. He also won the Coupe de France in 1990, scoring a goal in the final match. Blanc became, and remains, Montpellier's all-time leading goal scorer, with 84 in all competitions (76 in league play).

In 1991, Blanc tried a first experience abroad when he left Montpellier for Napoli in the Italian Serie A. Despite a decent season during which he managed to score six goals, he felt like he could not fully express his potential and returned to France after just one year, to Nîmes and then Saint Étienne, where again he not only imposed himself as one of the best defenders in the league, but also scored 13 goals in his last season with the latter club. Saint-Étienne, however, were struggling at the time and was almost relegated, only staying up because Marseille were not allowed to return to the first division because of the club's financial difficulties. Guy Roux, impressed by Blanc and looking for a replacement for Dutch international Frank Verlaat, convinced him to join Auxerre in 1995. Despite injuring himself early in the season, Blanc came back strongly and played a great part in the team's double that year.

Rolland Courbis managed to convince Blanc to join Marseille, which proved beneficial for both the club and Blanc. Blanc quickly became a leader in the team that was desperately lacking confidence, and helped Marseille finish an honorable fourth place in his first season, scoring 11 goals and earning the nickname Le Président (The President) in the process. The season following the World Cup was both successful and frustrating for Blanc and Marseille, as they finished runners-up in the championship, only one point shy of Bordeaux, and reached the UEFA Cupfinal, only to lose 3–0 to Parma, with Hernán Crespo intercepting Blanc's back pass to Stéphane Porato to score the opener. Afterwards, Blanc departed Marseille for Internazionale, where he enjoyed some success in defence, even winning the Pirata d'Oro (Inter Player of the Year) in 2000.

On 7 February 1989, he made his debut for the national team against Ireland. France, then in reconstruction after the retirement of numerous key players, did not manage to qualify for the 1990 World Cup. Shortly after that, they started an impressive 19-game unbeaten streak, including eight wins out of eight in Euro 1992 qualifying, making them one of the favorites to win the competition. They would, however, get knocked out in the pool stage by eventual winners Denmark.

France then entered the 1998 World Cup, which was held on home soil. Blanc was exemplary during the competition and, on 28 June 1998, scored the first-ever golden goal in World Cup history against Paraguay in the round of 16. In the quarter-final, Blanc helped France to a clean sheet over Italy and scored the winning penalty as Les Bleus prevailed in the shootout. He missed the final after being sent off in the semi-final against Croatia for elbowing Slaven Bilić, although replays showed that Bilić had clearly feigned the injury, earning the Croat heavy criticism afterwards. The sending off was the first (and only) red card of Blanc's professional career. Despite Blanc's absence, France lifted the World Cup for the first time after defeating Brazil 3–0 at the Stade de France. The two goals conceded during the tournament by France was a new record for a World Cup winner. This record was matched by Italy in 2006 and Spain in 2010.

Blanc was also part of the team that won Euro 2000 during which, despite having been criticised for his age and lack of speed during the qualifications, he proved reliable in defence and even scored France's first goal of the tournament against Denmark in the group stage. He announced his retirement from international football after the competition, following the example of his captain Didier Deschamps. On 2 September 2000, Blanc, along with Deschamps and Bernard Lama, played his final match for Les Bleus in a friendly against England at the Stade de France.[11]

Blanc was well known for kissing good friend and goalkeeper Fabien Barthez's head before the start of every match, supposedly for good luck (the two did repeat this ritual when they played together for Manchester United, but only for UEFA Champions League matches). The French national team was unbeaten in all matches when it fielded the World Cup and European Championship winning defence of Blanc, Desailly, Lilian Thuram and Bixente Lizarazu.[12] Overall, Blanc recorded 97 caps and scored 16 goals. In 1999, the readers of France Football magazine voted him the fourth best French player of all time behind Michel Platini, Zinedine Zidane, and Raymond Kopa.

On 16 May 2010, Blanc confirmed his departure from Bordeaux after three seasons in charge of the French outfit. After resigning from his position, Blanc contacted the French Football Federation to inquire about the France national team job, which was eventually vacated by Raymond Domenech following the 2010 World Cup. Later that day, FFF president Jean-Pierre Escalettes confirmed that Blanc was a candidate for the position. On 18 May 2010, with Blanc's appointment to the position becoming more probable, Bordeaux chairman Jean-Louis Triaud demanded compensation from the Federation. On 20 May 2010, the club reached an agreement with the FFF for €1.5 million.[15][16] On 26 June, French media confirmed that Blanc had signed a two-year contract with the Federation to lead the team to UEFA Euro 2012. The deal was finalized a week later and Blanc was officially named as manager of the team on 2 July.[17][18]

Blanc's first move as manager was to suspend all 23 players from the 2010 FIFA World Cupsquad from his first game, as collective punishment for a number of negative incidents involving the squad, which had occurred during the course of the competition.[19] He also reversed the policy on providing only halal meat at team lunches.[20] On 11 August, in his first game as manager, France lost 2–1 to Norway at the Ullevaal Stadion in Oslo.[21] However, Blanc's team soon managed to top their Euro 2012 qualifying group while also achieving friendly wins over England, Brazil and Germany. The first game of Euro 2012 was against England and ended in a 1–1 draw, after Samir Nasri scored to cancel out a goal scored by Joleon Lescott. France then went on to win their second game against Ukraine, thereby advancing to the quarter-finals despite losing to Sweden. France were eliminated in the quarter-finals after losing 2–0 to Spain. Blanc stepped down as manager of the national team on 30 June 2012.[22]